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Chemotherapy in Senior Adults

Chapter 08 – Cytotoxic and Targeted Anti-Cancer Treatment in the Senior Cancer Patient

Indications

In principle, the same indications for chemotherapy are present in older and younger cancer patients. There may, however, be specific concerns.

  • In curative settings, such as treatment of large-cell NHL, chemotherapy dose intensity is crucial. This type of NHL is aggressive with very poor prognosis if untreated. Soft/low-dose regimens have been shown to be clearly inferior to standard therapy but can still provide benefit to patients if standard therapy is too toxic.
  • In adjuvant settings of solid tumours, such as colorectal and breast cancer, the absolute benefits of chemotherapy are usually rather small and generally limited to 5% to 10% of patients, while all patients are exposed to potential toxicity. Moreover, the risks of chemotherapy increase with age, such as the risk of myelosuppression or cardiac failure with anthracyclines. It has also been shown that lowering the dose or dose intensity or choosing “soft” chemotherapy such as capecitabine for breast cancer is inferior to standard therapy. The decision of giving adjuvant chemotherapy is thus a delicate decision integrating the absolute risk of recurrence (based on tumour characteristics) and based on patient characteristics such as life expectancy, comorbidity, and the patient’s desire. If the decision is made to administer adjuvant chemotherapy, adequate dosing and regimens are warranted.
  • In metastatic settings of solid tumours, the goal is palliation and tumour control without causing excessive toxicity. Chemotherapy can be helpful, but continuous monitoring is required to ensure that toxicity is not taking the upper hand.

Considerations in the Use of Chemotherapy in Older Individuals

If the decision to give chemotherapy is made, it is important to keep in mind some specific age-related aspects summarised throughout this chapter.

Side Effects in Older Individuals

Elderly patients have a decreased tolerance to chemotherapy in general, with increased incidence of various toxicities. Some side effects are rather drug specific, such as cardiac failure with anthracyclines, or neuropathy with taxanes/cisplatin.

  • Myelosuppression is a more general side effect and is the major dose- limiting toxicity of many modern chemotherapeutic drugs. Initial retrospective analyses of data from clinical trials in patients with solid tumours showed no correlation between age and myelosuppression.
  • Treatment individualisation: Senior adults are the utmost example of heterogeneity, and adaptation to the individual situation is always required
  • Geriatric assessment: Geriatric assessment is the best way to obtain a more global view on the general health situation of the patient and is advised in all cancer patients > 70 years of age
  • Supportive or protective agent: Antiemetics, growth factors, pain killers, and anti-diarrhoeal drugs can be crucial to continue treatment
  • Risk of drug interactions: Polypharmacy is frequent in senior adults, and there is a great risk for drug interactions and potentially increased toxicity
  • Compliance: Compliance can be an important issue undermining the efficacy of chemotherapy (mainly for oral cytostatics) or potentially increasing toxicity (if supportive drugs are not taken appropriately at home)
  • Possibility of less toxic therapy: There might be good alternatives in some situations for chemotherapy, such as hormonal therapies, local radiotherapy, or surgery for localised problems
  • Maintain adequate hydration: Elderly patients have a tendency to drink less, especially when feeling ill, and are more intolerant of hydration. Poor hydration can lead to decreased clearance and increased toxicity, especially for drugs subject to renal excretion
  • Define the aim of chemotherapy: It is crucial to realise why chemotherapy is given. The need for maintaining dose and dose intensity can be very different depending on the setting
  • Renal function: Renal function declines continuously with ageing, and comorbidity can even further compromise renal function in the elderly. Moreover, many cytostatic drugs are renally excreted. If renal function declines and the same dose of chemotherapy is given, global exposition [e.g., as defined by area under the curve (AUC)] can markedly increase with accompanying increased toxicity. Dose adaptation, according to renal function, is thus mandatory to avoid excessive toxicity. The International Society of Geriatric Oncology (SIOG) has made specific guidelines on the determination of renal function in elderly, as well on dose adaptation of specific chemotherapeutic agents in renal dysfunction.
  • Be aware of pharmacological and clinical data for specific chemotherapy drugs: For most classical chemotherapeutic drugs, at least some data are available on age-related Pharmacokinetics and dosing (see also Tables below). Oncologists should be aware of these data, and take them into account when prescribing chemotherapy to older individuals. However, it should be stated that dose adaptation based on age-related pharmacological changes is an unvalidated approach since clinical trials prospectively testing the efficacy and toxicity of age-related dose adaptation versus standard dosing are lacking.

Considerations When Using Chemotherapy in Senior Individuals

Severe selection bias was present in these studies however, limiting the generalisation of these conclusions to the whole geriatric population. More recent data clearly show that the risk of neutropenia increases with age, for instance in NHL or breast cancer. Because of the increased risk of neutropenia and related complications in senior adults, and the potential for better outcomes when maintaining dose intensity in certain settings, prophylaxis with a colony-stimulating factor starting in the first cycle should be considered in elderly patients.

  • Mucositis (intestinal and/or oral) is a common side effect of several chemotherapeutic drugs, for example, irinotecan and 5-fluorouracil. Older persons appear to be more susceptible to this side effect, and aggressive and effective management of these and other side effects is crucial in senior adults.

Pharmacokinetic Parameters That Might Change with Ageing and Might Influence Efficacy/Toxicity of Chemotherapy

Parameter changesClinical consequences
Absorption: decreasedOral chemotherapy (e.g., capecitabine) might be less effective in elderly
Volume of distribution: decreasedSerum concentrations and toxicity of several chemotherapeutics might increase (e.g., cisplatin, taxanes, etoposide, irinotecan)
Hepatic metabolism: decreasedNot well known, may affect serum concentrations of chemotherapeutics eliminated by hepatic metabolism (e.g., taxanes, cyclophosphamide, anthracyclines)
Renal excretion: decreasedDosing should be adapted to present recommendations to avoid excessive serum concentrations and toxicity from renally excreted chemotherapeutics (e.g., carboplatin, topotecan, methotrexate)

Source: Courtesy of Elsevier.

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